T-cell acute lymphoblastic leukemia (T-ALL) is a blood malignancy afflicting mainly children and adolescents (Grabber et al., “Notch-1 Activation in the Molecular Pathogenesis of T-Cell Acute Lymphoblastic Leukaemia,” Nat Rev Cancer 6(5):347-59 (2006)). T-ALL patients present at diagnosis with elevated white cell counts, hepatosplenomegaly, and are at elevated risk for central nervous system (CNS) relapse (Aifantis et al., “Molecular Pathogenesis of T-cell Leukemia and Lymphoma,” Nat Rev Immunol 8:380-90 (2008) and Pui et al., “Current Management and Challenges of Malignant Disease in the CNS in Pediatric Leukemia,” Lancet Oncol 9:257-68 (2008)). For this reason, T-ALL patients usually receive cranial irradiation in addition to intensified intrathecal chemotherapy. The dramatic increase in survival is thought to be worth the significant side effects associated with this therapy. Such complications include secondary tumors, neurocognitive deficits, endocrine disorders and growth impairment (Pui et al., “Current Management and Challenges of Malignant Disease in the CNS in Pediatric Leukemia,” Lancet Oncol 9:257-68 (2008)). Unfortunately, little is known about the mechanism of leukemic cell infiltration on the CNS or how it can be prevented despite its clinical significance.
The present invention is directed to overcoming these and other deficiencies in the art.